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PubMed1981

[On the effect of imipramine on blood composition, glucose level and alkaline phosphatase activity of leucocytes in non-emotive Wistar rats and animals of inbred TMB strain (author's transl)].

The acute effect of imipramine (Tofranil) on the composition of blood, blood sugar level and activity of alcaline phosphatase in leucocytes was studied in an experiment with 30 adult male TMB-rats. These findings were compared with those in non-emotive Wistar rats (the scores without stress and under the condition of psycho-pharmacological effects) as far as corresponding motor activity in both strains was concerned. Hematological findings in a non-stress condition are considered to be identical in both strains studied. Under the acute effect of imipramine only about 50% of the compared parameters are similar to each other. The differing course of the hematological reaction within the other 50% points to the presence of non-identical control mechanisms in both strains.

Alkaline Phosphatase↗
PubMed1982

In vitro effect of haloperidol, chlorpromazine, imipramine and lithium on the erythrocyte catechol-O-methyltransferase.

Haloperidol, chlorpromazine, imipramine and lithium in concentrations similar to the average therapeutic plasma levels did not exert any in vitro inhibition on the erythrocyte catechol-O-methyltransferase (COMT). The inhibitory effects of haloperidol, chlorpromazine and imipramine were noted first at concentrations 1000-10 000 times their respective average therapeutic plasma levels. Unlike the former three psychotropic drugs, lithium exerted an in vitro inhibition already at a concentration 40 times the average therapeutic plasma level and that in a competitive way. The inhibitory effect of lithium could be neutralized by increasing the magnesium concentration, likewise in a competitive way.

Catechol O-Methyltransferase↗
PubMed1981

Uptake of 5-hydroxytryptamine by blood platelets incubated in plasma from rats and humans treated with amitriptyline and imipramine.

Blood platelets and [3H]-5HT ([3H]-5-hydroxytryptamine) were incubated in plasma samples taken from rats and humans treated with tricyclic antidepressants. The inhibition of 5-HT uptake detected in plasma was used as a bioassay of the drug concentration, and this was compared with gas chromatographic (GC) measurements of the same samples. With rats 5-HT uptake inhibition in plasma was studied one hour after five different doses of imipramine or amitriptyline i.p., and the time-course of uptake inhibition was studied from plasma samples taken 1, 2, 3 and 6 hours after injecting 10 mg/kg imipramine in to rats. Under long-term treatment, uptake inhibition was studied in samples taken from 20 patients treated with amitriptyline for 2 weeks or longer. In the samples with tricyclics, within the therapeutic range as detected by GC, the uptake inhibition was well over 50%. Bioassay based on uptake inhibition gave higher apparent results than did GC. The demethylated derivatives of the tricyclics, which were also measured by GC, did not explain the discrepancy. Thus, it is possible that other active metabolites formed in vivo also contribute to uptake inhibition.

Amitriptyline↗
PubMed1980

Withdrawal symptoms during the course of imipramine therapy.

The authors describe 2 cases in which withdrawal symptoms occurred during the course of imipramine therapy, after the patients had failed to take a single daily dose of medication. They note that similar withdrawal symptoms have been noted upon discontinuation of imipramine and its derivatives desipramine and chlorimipramine, but have not--with one exception--been reported in association with other tricyclics.

Adult↗
PubMedDate not supplied

Studies on the effect of cystamine on imipramine metabolism in radiation sickness.

Investigations were carried out for elucidating the effect of cystamine on the metabolism of imipramine in rats irradiated with a dose of 600 R. The investigations were based on determination of desmethylimipramine, the principal metabolite of this drug. It was found that cystamine reduced the serum imipramine level to control values but had no effect decreasing the level of desmethylimipramine. It caused also no fall in the concentration of this metabolite in brain tissue and even it raised this concentration. The authors explained these findings as a result of secondary resorption of desmethylimipramine into the blood stream, and a result of changed activity of beta-glucuronidase, these mechanisms being partly responsible for the overall effect.

Animals↗
PubMedDate not supplied

Cystamine effect on the pharmacokinetics of imipramine in radiation sickness.

Investigations were carried out on the effect of cystamine premedication (100 mg/kg) before irradiation with 600 R on imipramine (40 mg/kg) kinetics in male Wistar rats. It was found that cystamine prevented changes in blood imipramine level in the irradiated animals but it protected additionally the process of drug elimination from the blood (T 1/2 beta in controls = 1.67 h, in irradiated = 2.38 h, in irradiated premedicated = 4.01 h).

Animals↗
PubMed1980

Prolonged cholestasis and progressive hepatic fibrosis following imipramine therapy.

This report describes a middle-aged female who received imipramine for 7 days, developed severe cholestatic jaundice with features similar to primary biliary cirrhosis, and then improved clinically over the next 12 mo. Biochemical and histologic abnormalities persisted over a 14-yr period of follow-up, though subsequent administration of haloperidol may have influenced the long-term course. High levels of circulating immune complexes were also found 14 yr later, which raises questions about the relationship of primary biliary cirrhosis to drug-induced liver injury. A review of the literature on imipramine- and phenothiazine-related hepatic injuries reveals multiple similarities, and this case provides further evidence for a common hepatic reaction to the two drugs.

Antigen-Antibody Complex↗
PubMed1995

Treatment of chronic depression with sertraline or imipramine: preliminary blinded response rates and high rates of undertreatment in the community.

Despite the prevalence of chronic depression and its associated morbidity, there has been little systematic study of pharmacotherapy for this disorder. In this article, we report a preliminary analysis of the first 12-week phase of a multicenter clinical trial that will eventually include approximately 635 patients in acute, continuation, crossover, and maintenance studies of sertraline, a selective serotonin reuptake inhibitor (SSRI), and imipramine, a tricyclic antidepressant, for the treatment of chronic depression. Of the first 212 patients to enter the study, 168 completed all 12 weeks; of these, 61.3 percent were responders, including 58.9 percent of the 73 patients with chronic major depression and 63.2 percent of the 95 patients with double depression. Only 26.8 percent of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. In general, demographic and diagnostic characteristics were more similar than different for patients with chronic major and double depression. However, comorbid generalized anxiety disorder was significantly more common in patients with chronic major depression (11.2% threshold for chronic versus 4.9% threshold for double depression, p = .02). The results of this study provide preliminary evidence of the responsiveness of patients with chronic major or double depression to an SSRI or a tricyclic antidepressant.

1-Naphthylamine↗
PubMed1995

Use of imipramine hydrochloride for treatment of urospermia in a stallion with a dysfunctional bladder.

An 8-year-old stallion was evaluated because of recurrent urinary tract infections and chronic intermittent urospermia. After extensive diagnostic testing, it was hypothesized that the stallion had a reflex dyssynergia of the bladder and urethral sphincter. Initial attempts to manage the urospermia included semen fractionation, semen collection after voluntary urination, and use of semen extenders. None of these efforts reliably yielded a quality ejaculate. Administration of imipramine hydrochloride (1.2 mg/kg of body weight, PO, 4 hours prior to semen collection) was initiated in an attempt to enhance bladder neck closure during ejaculation. This treatment, combined with voluntary urination prior to ejaculation, resulted in ejaculates containing little or no urine. Using this protocol, 19 of 20 mares bred during the subsequent 2 years became pregnant. By the third year, the bladder dysfunction had progressed, and the urospermia was no longer manageable. Bladder catheterization, followed by manual expression of the bladder per rectum, were necessary prior to each semen collection to obtain a urine-free ejaculate. Three-and-a-half years after initial examination, transitional cell carcinoma of the bladder with metastasis was identified, and the stallion was euthanatized. It is not known whether the transitional cell carcinoma was related to the dysfunctional bladder. Imipramine hydrochloride did not eliminate, but did reduce, the frequency and degree of urospermia in the affected stallion for approximately 2 years.

Abdominal Neoplasms↗
PubMed1995

Primary nocturnal enuresis: a comparison among observation, imipramine, desmopressin acetate and bed-wetting alarm systems.

Patients with primary nocturnal enuresis were entered into 4 treatment groups: observation, imipramine, desmopressin acetate or alarm therapy. Patients were weaned from therapy 6 months after inclusion in the study and were evaluated for continence at 3, 6, 9 and 12 months after beginning the study protocol. Of the 50 patients under observation 6% were continent at 6 months and 16% were continent within 12 months. Of 44 patients treated with imipramine 36% were continent at 6 months on medication; however, only 16% were continent at 12 months, off medication. Similarly, of the 88 patients treated with desmopressin acetate 68% were continent at 6 months but only 10% were continent at 12 months. Of the 79 patients treated with alarm therapy 63% were continent at 6 months and 56% were dry at 12 months. Although each form of therapy improved continence over observation alone (p < 0.01), only the bed-wetting alarm system demonstrated persistent effectiveness (p < 0.001).

Adolescent↗
PubMed1994

Dose-response characterization of the antipanic effects of imipramine.

This article presents panic diary results of a dose-response study with imipramine hydrochloride in panic disorder with agoraphobia patients. Analysis of variance revealed significant time effects on panic frequency and severity measures, but group x time interaction effects were present for the severity measures only. Results also provided evidence for a positive dose-response relationship with 20 percent of patients in the placebo group, 31 percent in the low-dose group (0.5 mg/kg/day), 54 percent in the medium-dose group (1.5 mg/kg/day), and 70 percent in the high-dose (3 mg/kg/day) group being free of recurrent or severe panic attacks at posttreatment. Further stratified and logistic regression analyses revealed a direct linear relationship between total plasma tricyclic concentration and response. These findings affirm the dose-dependent nature and the specificity of imipramine's antipanic effects.

Dose-Response Relationship, Drug↗
PubMed1994

Adult respiratory distress syndrome and late death following imipramine overdose: a case report.

Adult respiratory distress syndrome (ARDS) after tricyclic antidepressant (TCA) overdose has been reported, but has not received as much attention in the literature as hemodynamic instability, cardiac arrhythmias or seizures. This report concerns a 33-year-old female who ingested a large amount of imipramine in an attempted suicide. She developed deep coma, hypotension, cardiac dysrhythmias and seizures. Although she survived initially, ARDS developed and she died of severe hypoxia nine days later. Her lung injury may have been the result of a variety of factors including prolonged hypotension, aspiration pneumonia, sepsis or a direct action on the lung parenchyma by imipramine. The literature pertaining to etiology, epidemiology, pathophysiology and management of TCA-induced lung injury has been reviewed. In one series of severe TCA overdose, an ARDS rate of 9% was reported. The risk of developing pulmonary edema and ARDS should be considered in severe TCA-poisoned patients. To try to prevent this complication, early intubation should be considered to avoid aspiration, and cautious volume loading, plus judicious use of alpha-adrenergic agonists, is indicated to prevent protracted hypotension.

Adult↗
PubMedDate not supplied

Prolonged administration of imipramine and (+)-oxaprotiline, but not citalopram, results in sensitization of the rat hippocampal CA1 neurons to serotonin ex vivo.

Prolonged (14 days, twice daily), but not acute, application of imipramine and (+)-oxaprotiline (10 mg/kg) induced sensitization of hippocampal CA1 neurons to the inhibitory effect of 5-hydroxytryptamine (5-HT), as studied ex vivo in the rat hippocampal slice preparation. Attenuation of the population spike, recorded in the CA1 pyramidal cell layer in response to stimulation of the Schaffer collateral-commisural pathway, was used to asses the sensitivity of neurons to 5-HT. Prolonged and acute administration of the selective 5-HT reuptake blocker citalopram did not change the responsiveness of hippocampal neurons to 5-HT. Since imipramine and (+)-oxaprotiline share the inhibitory effect on the norepinephrine reuptake, our results may indicate that long-term alterations in the noradrenergic system lead to modifications in postsynaptic serotonergic receptors.

Animals↗
PubMedDate not supplied

[Analgesic effect of imipramine in the treatment of ischium pain and circadian rhythm of cortisol release into the serum].

In the paper the results are presented of treatment of ischialgia with Imipramine, taking into account the circadian rhythm of cortisol release into the serum. The obtained results encourage to the use of tricyclic antidepressants in the treatment refractory cases of ischialgia. No significant differences were observed in the circadian rhythm of cortisol release into the serum before and after the treatment with Imipramine.

Adult↗
PubMedDate not supplied

[Psychotropic profile of essential antidepressants (amitriptyline, imipramine, desipramine, chlorimipramine): comparative study].

Comparative studies of the therapeutic activity of amitriptyline, imipramine, desipramine and chlorimipramine were studied in a group of 185 patients with endogenous depression. After standard 28-day treatment, the best results were obtained while using amitriptyline (improvement rate 67%, the greatest reduction in the Hamilton Depression Scale scored on 28-day of the treatment). The profile and characteristics of antidepressive action of all the drugs taken into consideration are comparable (including slightly more expressed sedative and deliberative effects of amitriptyline). Desinhibitive influence of desipramine and imipramine was not proved. Neither was tachythymoleptic activity of desipramine found. The study does not support the relation between the antidepressive action profile of tricyclic antidepressants and their influence on reuptake of monoamines (norepinephrine and serotonine).

Adult↗
PubMedDate not supplied

Open field behavior of rats reared in different social conditions: the effects of stress and imipramine.

Behavioral changes in rats divided on the weaning day into two groups (crowded and isolated) were studied in the computerized open field. At the end of the experiment the effects of an acute stress (1 h long immobilization) on open field behavior, body weight and body temperature, were examined. In a separate experiment both groups of rats were chronically pretreated with tricyclic antidepressant imipramine (5.0 mg/kg, po), and subsequently exposed to the same stress procedure. Social deprivation significantly enhanced spontaneous locomotion and exploratory activity. Restraint stress significantly decreased exploration, body weight and temperature, in the isolated animals only. Chronic pretreatment of rats with imipramine significantly attenuated the effect of stress on motor and exploratory behavior, as well as stress-induced changes in body weight and temperature, in the group of isolated animals. The present data indicate sensitization to stress of behavioral and vegetative processes in socially deprived animals. The relationship between rearing conditions and behavioral and vegetative reactivity to the environmental challenges is confirmed.

Acute Disease↗
PubMed1993

Cardiovascular effects of imipramine, fluvoxamine, and placebo in depressed outpatients.

BACKGROUND: The data presented represent cardiovascular parameters collected from one site of a larger, multicenter, double-blind, placebo-controlled, 6-week outpatient efficacy study of the serotonin uptake inhibitor fluvoxamine in depressed outpatients. METHOD: In this smaller study, we compared fluvoxamine (N = 17) to the prototypic antidepressant, imipramine (N = 14), and to placebo (N = 15). Specific parameters investigated were drug effects on postural pulse and blood pressure changes and ECG parameters including PR, QRS, and QTc intervals and ventricular heart rate. RESULTS: Fluvoxamine had few effects on measured parameters. Imipramine produced statistically significant changes on all measures; placebo had no effects on cardiac measures. CONCLUSION: Our data support that fluvoxamine, in a sample of healthy depressed outpatients, has little effect on cardiovascular function. Further study and clinical experience with this drug will be necessary before the full extent of its cardiac profile is known.

Adult↗